The big elephant in the room is the fact that the PDE-5 inhibitors have either come off patient or will be shortly. What is their status and what are the potential roadblocks to OTC status?
The PDE-5 inhibitors all remain prescription drugs. Generic versions of Viagra are being launched. We all know that PDE-5 inhibitors have some potential side effects—visual and auditory side effects—that occur in a very small percentage of patients but could be problematic if exposed to the general population. The real question concerns the stochastic use associated with erectile dysfunction versus a continual daily dose of Cialis, for instance, which is approved for daily-dose use for voiding dysfunction as well as erectile dysfunction.
We understand the mechanistics of the PDE-5 inhibitors for causing vasodilation, but if you functionally look at how they work, patients subjectively are better but there is no urodynamic correlate to that. Yes, there’s a slight improvement in flow rate, but you see no change in bladder contraction capabilities or bladder emptying. Some very interesting work done recently suggests that the PDE-5 effect, which can be a very significant subjective effect for some individuals, actually results from a spinal cord reflex mechanism (at least in rodents.)
Is there a possibility that they could be pushed for OTC use? Sure. The public certainly is aware of the class and certain agents in the class, and I think the public has had a recently positive experience with the PDE-5 inhibitors. But, again, because of the lack of true understanding of effect and the potential for both visual and auditory concerns, I think it’s going to be a bit of a safety hurdle.
There’s certainly been a lot of education directed to the public, but what about the nitrate issue?
The cardiac issue and the use of these drugs with nitrates is a substantial issue, and I think even experienced patients have trouble understanding that. So there will be a very significant self-selection concern.
Zithromax is available over the counter in the UK and Hiprex is available over the counter in Denmark. Do you see urinary antiseptics or antibiotics for UTI ever going OTC in the U.S.?
I say this self-ashamedly as a urologist, but we haven’t done a good job with institutionalizing treatment for urinary tract infections. A whole generation of physicians coming out of medical school don’t even understand the basics of urinary tract infection. We see a lot of overuse and abuse of antibiotics. We’re in a time of increasing antibiotic stewardship because of concerns related to antibiotic side effects. I personally have encountered quinolone-induced bacterial overgrowth, colonic bacterial overgrowth, and the sequelae of that.
The antiseptics and acidic agents such as methanamine hippurate may potentially provide a benefit for individuals who are prone to recurrent infections and are trying to self-medicate. The issue with methanamine hippurate concerns renal function and patients’ understanding of that. There are many people who don’t understand how bad the effect on renal functions is, and I think that’s critical.